IV infusion of a drag-reducing polymer extracted from aloe vera prolonged survival time in a rat model of acute myocardial ischaemia

Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 02/2007; 98(1):23-8. DOI: 10.1093/bja/ael307
Source: PubMed


I.V. infusion of drag-reducing polymers (DRPs) has been shown to improve survival time in animals subjected to haemorrhagic shock. We hypothesized that DRPs might prolong survival time in rats following acute myocardial ischaemia (AMI).
Sixteen adult male rats were anaesthetized and mechanically ventilated. An i.v. infusion of either Dextran-40 2.5% (Control, n=8) or Dextran-40 2.5% containing 50 microg ml(-1) of an aloe vera-based DRP (DRP, n=8) was initiated at 3.5 ml h(-1). The left anterior descending coronary artery was ligated. Blood pressure, skin-tissue perfusion, and heart rate were monitored and arterial blood samples were analysed.
The mortality at 60 min following coronary ligation was 0% in the DRP group vs 50% in the control group (P=0.025). DRP-treated animals maintained higher mean arterial pressure [60.9 (5.1) vs 47.5 (5.1) mm Hg, P=0.004] and tissue perfusion [4.2 (3.4) vs 1.2 (0.5) TPU, P=0.029]. The DRP group trended towards better acid-base status with base excess [-5.0 (1.7) vs -8.1 (5.1) mmol litre(-1), P=0.083] and pH [7.42 (0.07) vs 7.35 (0.02), P=0.03].
Administration of nanomolar concentrations of aloe vera-based DRP prolonged survival time in animals with AMI. DRPs may offer a novel method to treat organ/tissue hypoperfusion.

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Available from: Tetsuro Sakai, Mar 24, 2014
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    • "Infusion of DRP has been associated with increased survival after hemorrhagic shock [3,6,8], improved perfusion after myocardial infarction [5,25] or in the presence of a coronary artery stenosis [1,26], and reduced risk for atherosclerosis in areas with low shear stress [27,28]. The mechanism of how DRP influences perfusion is, however, not completely understood. "
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    ABSTRACT: Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion. We studied the effect of various concentrations of DRP on RBC distribution in more relevant round microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo. In round microchannels hematocrit was measured in parent and daughter branch at baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the plasma skimming effect in the daughter branch was eliminated, as parent and daughter branch hematocrit were equivalent, compared to a significantly lowered hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6 ± 1.7 µm. In the control group (saline, N=6) there was a significant increase in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5) reduced CFL significantly compared to corresponding baseline and the control group. After DRP administration the CFL reduced to about 85% of baseline at 5, 15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro findings demonstrate that DRPs induce a reduction in CFL width and plasma skimming in the microvasculature. This may lead to an increase of RBC flux into the capillary bed, and thus explain previous observations of a DRP mediated enhancement of capillary perfusion.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "According to Pacella's report, DRPs were shown to reduce microvascular resistance and improve perfusion to myocardium subserved by a flow-limiting coronary stenosis [12]. Additionally, a recent animal study has revealed that intravenous infusion of DRP extracted from aloe vera prolonged the survival time in a rat model of acute MI [11]. Mortality at 60 min after coronary ligation was 0% in the DRP group, vs 50% in the control group. "
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    ABSTRACT: Recent studies have shown that drag-reducing polymers (DRPs) prolonged survival time in rats with acute myocardial infarction (MI), but their effect on cardiac function post MI remains unknown. This study sought to test the hypothesis that intravenous infusion of DRPs may improve left ventricular (LV) function in rats following surgically induced MI. MI was induced by ligation of the left anterior descending coronary artery in 36 Sprague-Dawley rats, and sham operations were performed in 12 animals. DRPs were then administered to 18 of the MI rats. Echocardiograpy was used to evaluate the changes of impaired LV function and global wall motion. Besides, the hydrodynamic effect of DRPs on microcirculation was also assessed. The survival rate at 24h following MI was significantly different among the sham, MI and DRP groups (p = 0.023). DRP-treated animals had marked smaller left ventricular end-systolic diameter and better anterior systolic wall thickness comparison with untreated rats. Significant improvement of fractional shortening and ejection fraction were detected in MI rats with DRP. Wall motion score index and contrast score index were both significantly reduced by DRP treatment. DRPs were shown to have beneficial effects on microvascular variables including red blood cell velocity, diameter, blood flow and calculated wall shear stress in third-order arteriole. Acute administration of DRPs improved LV function in a rat model of MI possibly by improving microvascular blood flow due to their unique hydrodynamic properties. DRPs may offer a new approach to the treatment of coronary artery ischemic diseases.
    Full-text · Article · Feb 2011 · International journal of cardiology
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    ABSTRACT: We have shown that drag-reducing polymers (DRP) restore perfusion to a stenotic bed by lowering microvascular resistance. We studied whether resistance-lowering by DRP are due to changes in hydrodynamics or vasodilation. During intravital microscopy of rat cremaster muscle (n=18), DRP infusion increased aortic flow (p<0.002), decreased vascular resistance (p<0.01), increased arteriolar diameter (p=0.023), and increased RBC velocity in the arterioles (p<0.04), venules (p<0.003) and capillaries (p<0.02). To investigate whether DRP lowers resistance without involvement of shear (nitric oxide [NO])-mediated vasodilation, L-NAME was infused in 19 rats, but failed to abolish DRP resistance-lowering. To further investigate whether DRP resistance-lowering depends on vasodilation, adenosine was infused into rabbit femoral arteries (n=19) prior to DRP to achieve marked vasodilation. DRP caused an additional 14% decrease in femoral vascular resistance (p=0.022). DRP enhance microcirculatory perfusion by lowering vascular resistance. This involves not only some degree of shear-induced vasodilation, but also tone-independent resistance lowering mechanisms, suggesting that DRP favorably alter blood flow hydrodynamics. Modulation of blood flow hydrodynamics to enhance perfusion is unique, and may be of therapeutic value for any condition of compromised blood flow.
    No preview · Article · Jan 2009 · Biorheology
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